Dataset Information

Cyclic immonium ion of lactyllysine reveals widespread lactylation in the human proteome

ABSTRACT: Here we employed a non-enzymatic chemical labeling approach to introduce lactylation on lysine residues of model peptides and proteins. Tandem MS acquisition of lactylated peptide carriers on different MS platforms unequivocally led us to note an intense peak corresponding to the “cyclic” immonium ion of lactyllysine that is generated from the “linear” immonium ion upon the loss of NH3. The cycIm ion provides superior sensitivity and specificity as a lactylation marker than the linIm ion. Together, the ability to confidently identify protein lactylation empowers mapping the landscape of human lactylation proteome and fosters ensuing investigation into the regulatory mechanisms of lactylation when our understanding to this newly discovered PTM is still during its infancy.

ORGANISM(S): Homo Sapiens

SUBMITTER: Hui Ye

PROVIDER: PXD028488 | iProX | Wed Sep 15 00:00:00 BST 2021

REPOSITORIES: iProX

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Cyclic immonium ion of lactyllysine reveals widespread lactylation in the human proteome.

Wan Ning N Wang Nian N Yu Siqin S Zhang Hanqing H Tang Shuo S Wang Dexiang D Lu Wenjie W Li Huanhuan H Delafield Daniel G DG Kong Ying Y Wang Xinmiao X Shao Chang C Lv Langlang L Wang Guangji G Tan Renxiang R Wang Nanxi N Hao Haiping H Ye Hui H

Nature methods 20220627 7

Lactylation was initially discovered on human histones. Given its nascence, its occurrence on nonhistone proteins and downstream functional consequences remain elusive. Here we report a cyclic immonium ion of lactyllysine formed during tandem mass spectrometry that enables confident protein lactylation assignment. We validated the sensitivity and specificity of this ion for lactylation through affinity-enriched lactylproteome analysis and large-scale informatic assessment of nonlactylated spectr ...[more]

PMID: 35761067

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Project description:Lysine lactylation (Kla) is a newly discovered histone post-translational modification (PTM), playing important roles in regulating transcription in macrophages. Increasing evidence demonstrates that lysine lactylation plays an important regulatory role in metabolic processes in both bacterial and human cells. However, little is known about the extent and function of lysine lactylation in fungi, here investigated with the black yeast Phialophora verrucosaverrucose as a model organism. WeHere, we report the first proteomic survey of this modification in P. verrucosa. We performed a global lactylation analysis of P. verrucosa using high accuracy bottom-up nano-LC-MS/MS in combination wwith the enrichment of lactylated peptides from digested cell lysates and subsequent peptide identification. In total, 636 lactylation sites on 420 lactylated proteins were identified in this pathogen, of which contained in 26 types of modification motifs. Our results show that over 85% of lactylated proteins were distributed in cytoplasm, mitochondria, and nucleus. The identified proteins were found to be involved associated toin diverse biological processes and were significantly enriched in the melanin biosynthesis process. Most strikingly, Kla was found in 23 structural constituent proteins of ribosome, indicating an impact of Kla in protein synthesis . Moreover, 12 lactylated proteins participated in fungal pathogenicity, suggesting a potential role for Kla in this process. Protein interaction network analysis suggested that a mass of protein interactions are regulated by lactylation. Together, our findings reveal widespread roles for lysine lactylation in regulating metabolism and melanin biosynthesis in P. verrucosa. Our data provide a rich resource for functional analyses of lactylation and facilitate the dissection of metabolic networks in this pathogen. The combined data sets represent the first report of the lactylome of P. verrucosa and provide a good foundation for further explorations of Kla in clinical fungal pathogens.

Dataset Information

Cyclic immonium ion of lactyllysine reveals widespread lactylation in the human proteome

Publications

Cyclic immonium ion of lactyllysine reveals widespread lactylation in the human proteome.

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